Institut Pasteur

Centre National De La Recherche Scientifique

Thomas Jefferson University

Institut National De La Sante Et De La Recherche Medicale

Université Pierre Et Marie Curie (paris 6)

Université Pierre Et Marie Curie

Christophe Prehaud

Monique Lafon

Pierre Lafaye

Matthias Johannes Schnell

Nicolas Wolff

Zakir Khan

Elouan Terrien

Sandrine Vitry

Pierre-Emmanuel Ceccaldi

Philippe Afonso

The invention is in the domain of delivery of molecules to brain cells across the blood-brain barrier. The invention relates to a novel polypeptide-based carrier that allows the efficient delivery of an effector peptide, to neuron cells across the blood-brain barrier, and to methods for the production and testing of such carrier, including a model for testing the capacity of such molecule to cross the blood-brain barrier and/or the toxicity of molecules on the blood brain barrier and/or the capacity of molecules that have crossed to target human brain cells (e/g. neurons, astrocytes and microglial cells).

Nanobodies suitable for neuron regeneration therapy

The invention is in the domain of delivery of molecules to brain cells across the blood-brain barrier. The invention relates to a novel polypeptide-based carrier that allows the efficient delivery of an effector peptide, to neuron cells across the blood-brain barrier, and to methods for the production and testing of such carrier, including a model for testing the capacity of such molecule to cross the blood-brain barrier and/or the toxicity of molecules on the blood brain barrier and/or the capacity of molecules that have crossed to target human brain cells (e.g. neurons, astrocytes and microglial cells).

In vitro blood-brain barrier model

The invention relates to polypeptides containing a cytoplasmic domain ending with a MAST-2 binding domain, from 11 to 13 residues, the first two residues of which are S and W, and the last four residues of which are Q, T, R and L, the polypeptides presenting a high affinity for the PDZ domain of the human MAST2 protein. The invention also relates to polynucleotides, vectors, lentiviral particles, cells as well as compositions containing the same. The invention is also directed to the use of the polypeptides, polynucleotides, vectors, lentiviral particles, cells and compositions in the treatment and/or prevention of a disease, disorder or condition, which alters the Central Nervous System (CNS) and/or the Peripheral Nervous System (PNS). The invention also concerns molecular signatures of cellular genes to determine the neurosurvival and/or neuroprotection activity of a molecule.

High MAST2-affinity polypeptides and uses thereof

The invention demonstrates that, contrary to apoptotic rabies virus G proteins, certain non-apoptotic rabies virus G proteins, such as the G protein of the CVS-NIV strain, have a neurite outgrowth promoting effect. The invention further demonstrates that this neurite outgrowth promoting effect is due to the cytoplasmic tail of the non-apoptotic rabies virus G proteins, more particularly to their PDZ-BS, which shows a single-point mutation compared to the one of apoptotic rabies virus G proteins. The invention provides methods for inducing and/or stimulating neurite outgrowth, which are useful in inducing neuron differentiation, for example for the treatment of a neoplasm of the nervous system, as well as in regenerating impaired neurons, for example for the treatment of a neurodegenerative disease, disorder or condition or in the treatment of a microbial infection, or in protecting neurons from neurotoxic agents or oxidative stress.

Neuron generation, regeneration and protection

The invention demonstrates that, contrary to apoptotic rabies virus G proteins, certain non-apoptotic rabies virus G proteins, such as the G protein of the CVS-NIV strain, have a neurite outgrowth promoting effect. The invention further demonstrates that this neurite outgrowth promoting effect is due to the cytoplasmic tail of said non-apoptotic rabies virus G proteins, more particularly to their PDZ-BS, which shows a single-point mutation compared to the one of apoptotic rabies virus G proteins. The invention provides means for inducing and/or stimulating neurite outgrowth, which are useful in inducing neuron differentiation, for example for the treatment of a neoplasm of the nervous system, as well as in regenerating impaired neurons, for example for the treatment of a neurodegenerative disease, disorder or condition or in the treatment of a microbial infection, or in protecting neurons from neurotoxic agents or oxidative stress.

Growing community of inventors

Guyancourt, France

Christophe Prehaud